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JEPonline
Attenuation of Dyspnea and Improved Quality-of-Life through Exercise Training in Patients with COPD
Rick Carter1, Brian Tiep2, Yunsuk Koh3
¹Lamar University, Beaumont, TX, ²Respiratory Disease Management Institute, Monrovia, CA, ³Baylor University, Waco, TX
ABSTRACT
Carter R, Tiep B, Koh Y. Attenuation of Dyspnea and Improved Quality-of-Life through Exercise Training in Patients with COPD. JEPonline 2016;19(1):1-16. This study evaluated changes in dyspnea and health-related quality of life (HRQOL) before and after exercise training in a COPD cohort. One hundred and twenty-six patients with moderate to severe COPD (%PredFEV1 = 45.9 ±12.5%) were evaluated before and after 16 wks of exercise training (ET). Patient assessments included: pulmonary function tests; gas exchange; cycle ergometry (CE); arm ergometry (AE); and the 6-min walk test (6MWT) with dyspnea measured using Borg scores and with the multidimensional Chronic Respiratory Disease Questionnaire (CRQ). Following ET, work performance was significantly increased for CE, AE, and the 6MWT (P<.0001) and these changes were considered clinically significant. Borg scores at peak exercise decreased for CE (–0.95 ± 2.8 units, P<.003); AE (-0.8 ± 2.6 units, P<.02), and 6MWT (-0.5 ± 2.3 units, P<.05) with greater work output. Borg scores for CE and AE at isotime demonstrated significant improvement (CE – 1.4 ± 2.0, P<.0001 & AE – 1.0 ± 2.1, P<.0001). Statistically significant and clinically relevant improvements in CRQ dyspnea (7.00 ± 5.76 (P<.0001)); emotional function (4.5 ± 6.3, P<.0001); fatigue (4.1 ± 4.1 P<.0001); mastery 3.1 ± 3.5, P<.0001), and total CRQ score (20.0 ± 15.9, P<.0001) were observed. The data suggest that a 13-watt or 12-watt or greater increase for CE and AE, respectively, represents clinically significant improvements. Exercise training improves upper and lower extremity work performance and reduces dyspnea during exercise while improving overall quality-of-life.
Key Words: Dyspnea, COPD, Exercise, HRQOL, 6MWT
INTRODUCTION
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide, with an escalating prevalence of more women than men (7,44). Patients with COPD suffer from several symptoms that adversely affect general health and quality-of-life (36). Identifying optimal methods for assessing COPD, making appropriate medical diagnosis and evaluating clinical outcomes remains somewhat controversial (56). Objective pulmonary function measurements, such as the forced expiratory volume in one second (FEV1), provide important and timely information regarding the correct diagnosis, stage severity, and prognosis of COPD.
For patients with COPD, dyspnea is a key complaint that is causally interrelated with impaired exercise capacity by creating a major barrier to the patient’s ability to live an active life. Dyspnea-on-exertion limits functional ability and is associated with depression and anxiety in promoting disability and negatively impacting health-related quality of life (HRQOL) (58). Further, dyspnea is typically the symptom that brings the patient to the physician.
In the clinical setting the assessment of dyspnea has gained a functional role for not only determining how short-of-breath an individual may be under a variety of conditions, but also to monitor the patient’s response to therapy (63). While there are several approaches and multiple instruments for measuring dyspnea, a few have gained popularity in their ability to assess different aspects of dyspnea. For example, the chronic respiratory questionnaire (CRQ) is a quality-of-life instrument that includes a dyspnea measurement domain while Borg scores are routinely used to assess dyspnea during exertion (5,30,68). Generally, these instruments all purport to assess dyspnea, the Borg scale measures dyspnea during exertion when the rise of work of breathing reflects the increasing disparity between the decreased ventilator capacity and the increasing ventilatory requirement. However, little attention has been devoted to investigating changes in dyspnea using multiple instruments before and following exercise training in patients with COPD for both arm and leg exercises. Additionally, there is a scarcity of comparison data available for dyspnea scores collected during formal exercise testing with a cycle egometer or treadmill against that acquired during the 6-min walk test (6MWT). Because so many different assessments and exercise paradigms exist, a study where all measures are obtained in the same cohort may help explain the findings when only one set of data are available.
We hypothesized that patients may reflect dyspnea differently depending on the context and/or the stress encountered to invoke dyspnea and that exercise training will reduce the sensation of dyspnea differently depending on the instrument used for assessment. This study seeks to quantify self-reported dyspnea, using multiple instruments before and following exercise rehabilitation, when medical delivery is optimized. Further, the impact of exercise induced changes in physiologic function will be evaluated for arms and legs and by use of field testing (6-min walk) to further explore their interaction with Borg scores and HRQOL indices. Lastly, based on the exercise training schema used, we wanted to determine if any of the changes associated with exercise training could be considered as a clinically significant.
METHODS
Subjects
One hundred twenty-six COPD patients in stable condition (92 males and 34 females; mean age and range, 66.8 ± 7.3 yrs and 46 to 80 yrs, respectively) volunteered to participate in this study. Informed consent was obtained following the guidelines established by the Institutional Ethics Committee. All subjects: (a) had a history of COPD (emphysema or bronchitis); (b) were in stable medical condition with no acute exacerbations during the 3 months prior to the study; (c) were able to engage in exercise; and (d) were mentally suited for completion of the protocol. The exclusion criteria included: (a) acute or chronic heart disease that would limit exercise; (b) primary diagnosis of asthma; (c) significant vascular or metabolic problems; (d) a bleeding disorder; or (e) the inability to give informed consent.
Severity of pulmonary dysfunction ranged from moderate to severe (20). Prior to exercise testing, the subjects’ medication regime was optimized by a pulmonologist. All subjects were instructed to use their medications as prescribed. They were told to use their bronchodilator therapy 30 min prior to exercise testing or training. Pre- and post-bronchodilator evaluations were performed and dyspnea ratings obtained in the post-bronchodilator condition. Subjects who were hypoxemic were tested without supplemental oxygen during the gas exchange studies and during the 6-min walk. Oxygen was administered at a liter flow setting to minimize desaturation for 9 subjects.
Pulmonary Function Tests
Spirometry was performed with a SensorMedics Vmax 20C spirometry system (SensorMedics, Yorba Linda, CA) that was calibrated prior to each test and compared to the predicted values of Crapo (18). Lung diffusion capacity for carbon monoxide (DLCO mL·min-1·mmHg-1) was measured by the single breath technique of Jones and Mead (34) using a SensorMedics system (SensorMedics, Vmax 22, Autobox, Yorba Linda, CA). Lung volumes were determined by body plethysmnography (SensorMedics, Vmax 22, Autobox, Yorba Linda, CA). Lung diffusion capacity for carbon monoxide (DLCO) was compared to the data from Miller et al. (48) while normal predicted lung volumes were derived from the equations of Goldman and Becklake (23) (females) and of Boren et al. (4) (males). All studies were performed post bronchodilation following Albuterol (90 mcg x 2) administration via a meter dose inhaler (MDI). Pulmonary function testing and severity classification was performed following the standards outlined by the ERS-ATS (20).
Exercise Testing
All subjects performed an incremental arm test (5 to 15 watts·min-1 square wave adjustment) to a symptom limited peak work capacity. The difference in workload selected was based on predicted functional capacity and a desire to exercise patients for about 9 min total; the higher the functional predicted capacity the higher the initial workload selected. A modified Monarch arm crank ergometer (Quinton Instruments, Bothell, WA) was used to deliver precise arm workloads. Each subject was given a 3-min 0 load accommodation period followed by a 5 to 15 watts·min-1 increment in workload adjustment to a symptom limited peak. Gas exchange data were obtained using the instrumentation described below. Borg dyspnea scores were obtained at the end of each minute of exercise.
For the leg exercise test, the subjects peddled on an electronically braked cycle ergometer (CE) (Medical Graphics, Minneapolis, MN) according to a ramp protocol as described by Wasserman and Whipp (65). Again, the workload selected was based on predicted values so that about 9 min of exercise would maximize the performance. The arm and leg exercise tests were separated by at least 2 hrs of rest and 30 min following bronchodilator therapy. Both leg and arm ergometry testing were completed prior to the 6-min walk test, which was completed 1 to 2 d later.
To evaluate dyspnea during exercise, we used isotime at 4 min using identical exercise testing protocols with the subjects. This comparison allowed for changes in both physiological function and dyspnea to be evaluated within each subject. Thus, each subject served as his or her own control.
Gas Exchange Measurement
Following a detailed explanation of the testing procedure and a practice trial pedaling/cranking, all subjects were prepared for testing using standard procedures (8). Normal predicted values were computed according to the method of Wasserman and Whipp (64). Peak predicted VE was estimated from the measured FEV1 using the method of Carter and colleagues (11). Heart rate was calculated using the R-R ECG intervals.
6MWT
We conducted the 6MWT as described by Guyatt et al. (28,29), which is a modification of the 12-min walk test originally described by McGavin et al. (47). A 100 foot (30.5 m) hospital corridor course was used and marked by colored tape at each end of the corridor. Subjects were instructed to walk from end to end at their own pace, while attempting to cover as much distance as possible in the allotted 6-min. A research assistant timed the walk and recorded the distance traveled, rating of perceived exertion (RPE) for dyspnea and leg fatigue, heart rate and SpO2 for each minute of walking completed. For subjects requiring supplemental oxygen (9 patients), the research assistant carried the portable oxygen cylinder during the walk and oxygen was titrated to maintain SpO2 above 90%.
Assessment of Dyspnea
Direct Measures of Dyspnea — Borg Scores
A modified Borg scale was used to measure perceived breathlessness/dyspnea (1,6,24,69). The modified Borg scale administered in this study has been used extensively in exercise related studies, and it is known to be a valid, reliable, and sensitive instrument to change (37,41,59). Two Borg score ratings were used in the evaluation of exercise dyspnea. The first was obtained at peak exertion. The second was rated at the end of the 4th min of exercise (isotime Borg score) using identical testing protocols for baseline and post-exercise. Thus, the subject was evaluated at the same workload prior to and following rehabilitation. The 4th min (isotime) of exercise was selected from the first exercise study to compare identical workloads for rating dyspnea and other important physiologic indices before versus after training. This selection reflects the limited work capacity anticipated for subjects with moderate to severe COPD prior to training and a work output that would be modified with training and is in line for expected activities of daily living energy costs.
Chronic Respiratory Disease Questionnaire (CRQ)
The chronic respiratory disease questionnaire (CRQ) is a reliable and valid disease specific measurement tool for evaluating Health Related Quality-of-life (HRQL) in patients with respiratory disease (15). It was developed in 1987 by Guyatt et al. (26) for the assessment of quality-of-life for patients with lung disease. It evaluates four dimensions of HRQL including dyspnea, emotional function, fatigue, and mastery. The subjects were asked to select the five most bothersome activities that elicited breathlessness and/or dyspnea during the preceding 2 wks. Severity of dyspnea was measured by selecting numeric values ranging from 1 [extremely short of breath] to 7 [not at all short-of-breath]. Individual scores were then summed to derive an overall CRQ dyspnea score (range 5 to 35), with 5 representing the most severe dyspnea and 35 the least significant dyspnea. An important aspect of the CRQ is its ability to quantify clinically important change resulting from an intervention. A change of 0.5 for each item represents a clinically important change (33). Thus, for dyspnea a change of greater than 2.5 (0.5 x 5 questions) would be clinically significant. The same scoring holds for fatigue (0.5 x 4), emotional function (0.5 x 7), and mastery (0.5 x 4).
Exercise Training
The exercise training program consisted of a supervised training program that included treadmill walking, leg cycling, arm cranking, light arm weights ( 1 to 2 lbs), and arm and leg ergometry using a Schwinn Airdyne® cycle. The subjects exercised 3 times·wk-1 for 16-wks at 20 to 60 min·session-1 depending on individual ability as measured during the initial exercise testing. Intensity of training was derived from the subjects’ estimated or measured anaerobic threshold from their initial exercise test for arms and legs, respectively. When the subjects were just initiating training the workloads were set at approximately 80% of their anaerobic threshold. All subjects completed the 20 min of exercise trainig at multiple stations. Duration of training was increased as tolerated till 40 min of exercise training could be completed. Thereafter, intensity was increased as tolerated so as to maintain the 40-min exercise training duration.
Clinically Significant Changes in Work Performance
Because the subjects were evaluated using several testing modalities, it was important to identify if any of the reported changes were considered as clinically significant. To address this issue, the 6MWT was used, as the surrogate, for investigating corresponding changes in arm and leg ergometry. Using the data from Toosters and colleagues (61) for a clinically meaningful change, we extrapolated the 6 MWT data to that obtained for the bike and arm crank. From these comparisons, an attempt was carried out to identify the minimal threshold for clinically significant changes.
Statistical Analysis
Descriptive statistics (mean ± SD ) was used to calculate variables of interest using the Statistical Analysis System for Windows version 8E (The SAS Institute, Cary, North Carolina). Parametric (Pearson) and non-parametric (Spearman) correlations were used to evaluate the relationship of one variable to another. Paired t-tests were used to determine if significant differences exist within an individual over time (paired t-test). All data are presented as mean ± SD and a value of P<.05 was considered significant.